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Supplemental Figure legends: Supplemental Figure 1. The quality of naïve courtship behavior of 5 day-old and 45 day-old wild type flies (Ore R). The quality of naive courtship that was performed by Ore R male flies was analyzed by binning the number of males that advanced to particular phases of courtship (McBride et al., 2005; Orgad et al., 2000). At 45 days of age there is no significant change in naïve courtship behavior compared to that at 5 days of age. Supplemental Figure 2. The locomotor behavior of 7-10 day-old and 34-37 day-old wild type flies (Ore R). Locomotor activity was measured by line crossing (Griffith et al., 1993; McBride et al., 2005). There was no difference in spontaneous locomotor activity between the two ages of WT flies that were examined. Supplemental Figure 3. The quality of naïve courtship behavior of 5 day-old psn-het flies. (A-B) The quality of naïve courtship that was performed by psn-het male flies was further analyzed by binning the number of males that advanced to particular phases of courtship for 5 day-old psn-het males. No differences between the quality of courtship in young adult psn-het flies and young adult WT flies were observed (compare to Figure S1). Supplemental Figure 4. The locomotor behavior of 7-10 day-old psn-het flies. Locomotor activity was measured by line crossing (Griffith et al., 1993; McBride et al., 2005). There were no differences in spontaneous locomotor activity between any of the psn-het genotypes or WT flies (compare to Figure S2). 1 Supplemental Figure 5. The quality of naïve courtship behavior of 34-37 day-old psn-het flies. (A-B) The quality of naïve courtship that was performed by male flies was further analyzed by binning the number of males that advanced to particular phases of courtship for 34-37 day-old psn-het males. No differences between the quality of courtship in older adult psn-het flies compared to young 7-10 day old adult psn-het flies or young and old WT flies were observed (compare Figures S1 and S3). Supplemental Figure 6. The locomotor behavior of 34-37 day-old psn-het flies. Locomotor activity was measured by line crossing (Griffith et al., 1993; McBride et al., 2005). There were no differences in spontaneous locomotor activity between any of the psn-het genotypes, or from the younger 7-10 day old psn-het flies or young and old WT flies (compare to Figures S2 and S4). Supplemental Figure 7. Genetic interaction between dfmr1 and presenilin. A) Heterozygous loss of dfmr1 enhances the phenotype of heterozygous loss of psn in naïve courtship at 5 days of age. All of the flies naïve courtship indices are shown relative to their individual genetic backgrounds. The psn[B3]/+ naïve courtship was not different from the Ore R background naïve courtship. The dfmr1/+ line also shows courtship that is not different from the w- background. However, flies that are transheterozygous being both psn +/- and dfmr1 +/(psn[B3], +/+, dfmr1) display severe impairments in naïve courtship. This impairment in naïve courtship is rescued when the transheterozygous flies additionally contain a WT dfmr1 insertion, 2 (WT rescue; psn[B3], +/+, dfmr1). The dfmr1 mutant and transgenic lines are described in Dockendorff et al., 2002. Supplemental Figure 8. Pharmacologic treatments with lithium and LY341495 do not correct agedependent impairments in short-term memory in Parkinson’s model flies at 30 days of age. Mean CIs (+/- SEM) are plotted, Ns are indicated above each bar for all groups. The levels of significance are indicated (one asterisk * indicates p < 0.05, two asterisks ** indicate p < 0.01, three asterisks *** indicate p < 0.001). A) Flies carrying one copy of the wild type human UASalpha synuclein gene (UAS-Syn) (Feany and Bender, 2000) or one copy of the 30Y-Gal4 driver had intact short-term memory at 30 days of age. B) Flies expressing alpha synuclein in the mushroom bodies under the control of the 30Y driver had intact short-term memory at 5 days of age, but impaired short-term memory at 30 days of age. C) Treatment with the mGluR antagonist LY341495 (LY) or lithium (Li), or D) MPEP from age 6-29 days of age did not prevent the agedependent impairment in short-term memory as observed at 30 days of age. Supplemental Table 1. The psn alleles used in this study and the molecular lesion in the allele. 3 Supplemental Literature Cited. Deak, P. , Omar, M. M. , Saunders, RDC., Pal, M., Komonyi, O., Szidonya, J., Maroy, P., Zhang, Y., Ashburner, M., Benos, P., Savakis, C., Siden-Kiamos, I., Louis, C., Bolshakov, V. N., Kafatos, F. C., Madueno, E., Modolell, J. and Glover, D. M. (1997). PElement Insertion Alleles of Essential Genes on the Third Chromosome of Drosophila Melanogaster: Correlation of Physical and Cytogenetic Maps in Chromosomal Region 86E-87F. Genetics 147, 1697–1722. Feany, M.B., and Bender, W.W. (2000). A Drosophila model of Parkinson's disease. Nature 404, 394-398. Griffith, L.C., Verselis, L.M., Aitken, K.M., Kyriacou, C.P., Danho, W., and Greenspan, R.J. (1993). Inhibition of calcium/calmodulin-dependent protein kinase in Drosophila disrupts behavioral plasticity. Neuron 10, 501-509. McBride, S.M., Choi, C.H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K.K., Dockendorff, T.C., Nguyen, H.T., et al. (2005). Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45, 753-764. Orgad, S., Rosenfeld, G., Greenspan, R.J., and Segal, D. (2000). courtless, the Drosophila UBC7 homolog, is involved in male courtship behavior and spermatogenesis. Genetics 155, 1267-1280. 4